{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:01:41Z","timestamp":1777395701077,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,9,27]],"date-time":"2007-09-27T00:00:00Z","timestamp":1190851200000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p><jats:bold><jats:sc>Abstract<\/jats:sc>:\u2002<\/jats:bold>  <jats:bold>Dehydroepiandrosterone (DHEA) has attracted much interest because of its many antiaging, metabolic and immune\u2010modulating effects in rodents. Synthetic derivatives, such as 5\u2010androstene\u201016\u03b1\u2010fluoro\u201017\u2010one (HE2500) and certain natural metabolites also provide benefit in various animal models of autoimmune and metabolic diseases. But, like DHEA, low potency and low oral bioavailability suggested limited usefulness of these compounds in humans. We hypothesized that HE3286, a novel 17\u2010ethynyl derivative would be orally bioavailable, more potent, and chemically more useful in man than its parent compound. We found that on a dose\/mass basis, HE3286 demonstrated up to 25% oral bioavailability in mice. In the DBA mouse model of collagen\u2010induced arthritis (CIA), animals receiving oral treatment with HE3286 (50 mg\/kg), beginning at onset of disease, significantly decreased CIA peak scores and daily severity of arthritis scores. Benefit was associated with decreases in: (1) production of TNF\u2010\u03b1, IL\u20106, and IL\u201017; and (2) decreases in joint inflammation, erosion, and synovial proliferation as judged by histological analysis. HE3286 was not found to be immune suppressive in any of the classical models tested, including mitogen\u2010induced proliferation, delayed\u2010type hypersensitivity, or mixed lymphocyte reaction. Instead, benefit was associated with increases in numbers and function of CD4+CD25+FOXp3+CD127\u2013 regulatory T cells (T<jats:sub>reg<\/jats:sub>). To our knowledge, this is probably the first study to report that an orally bioavailable synthetic analogue of DHEA can ameliorate ongoing disease in a CIA mouse model with relevance to rheumatoid arthritis (RA) and to correlate that finding with decreases in proinflammatory cytokines and increases in T<jats:sub>reg<\/jats:sub> cells. Hormones targeting T<jats:sub>reg<\/jats:sub> cells hold the intriguing potential to treat autoimmune, infectious, and neoplastic diseases.<\/jats:bold> <\/jats:p>","DOI":"10.1196\/annals.1423.066","type":"journal-article","created":{"date-parts":[[2007,10,2]],"date-time":"2007-10-02T20:20:20Z","timestamp":1191356420000},"page":"630-640","source":"Crossref","is-referenced-by-count":35,"title":["A New Orally Bioavailable Synthetic Androstene Inhibits Collagen\u2010Induced Arthritis in the Mouse"],"prefix":"10.1111","volume":"1110","author":[{"given":"D.","family":"AUCI","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"KALER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"SANDHYA","family":"SUBRAMANIAN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YUGIN","family":"HUANG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"FRINCKE","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"READING","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"OFFNER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,9,27]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5867"},{"key":"e_1_2_5_3_2","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.4049\/jimmunol.161.7.3589","article-title":"Characterization of a peptide analog of a determinant of type II collagen that suppresses collagen\u2010induced arthritis","volume":"161","author":"Myers L.K.","year":"1998","journal-title":"J. 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